The invention relates to medical articles having components that have been modified with a compound that stimulates cell adhesion, such as a structural protein or a polypeptide growth factor. The invention further relates to methods for producing these medical articles.
Prostheses, i.e., prosthetic devices, are used to repair or replace damaged or diseased organs, tissues and other structures in humans and animals. Prostheses must be generally biocompatible since they are typically implanted for extended periods of time. Prostheses can be constructed from natural materials such as tissue, synthetic materials or a combination thereof. For example, prostheses, such as mechanical heart valve prostheses, are manufactured from biocompatible metals and other materials, such as pyrolytic carbon coated graphite and polyester. Mechanical heart valves generally include an occluder that pivots within an orifice ring, through which blood flows. Pivoting of the occluder opens and closes the valve.
Although mechanical heart valves have the advantage of proven durability through decades of use, they are associated with a potential for blood clotting on or around the prosthetic valve. Blood clotting can lead to acute or subacute closure of the valve or associated blood vessel. For this reason, patients with implanted mechanical heart valves remain on anticoagulants after implantation of the valve. Anticoagulants impart a potential risk of significant bleeding complications and cannot be taken safely by certain individuals. Occluders and orifice rings of mechanical heart valves can be formed from materials, such as pyrolytic carbon, that reduce the risk of blood clotting by the nature of their relative thromboresistance.
In addition to heart valve prostheses formed with rigid occluders, heart valve prostheses can be constructed from tissue or flexible polymer materials. Thrombosis and calcification are concerns associated with polymer heart valves. Tissue-derived prosthetic heart valves generally have blood flow characteristics and surface properties that provide a high degree of thromboresistance without the need for anticoagulant therapy. Therefore, thrombosis or thromboembolism and bleeding complications are less likely to occur than with mechanical heart valves. Unfortunately, prosthetic tissue heart valves are limited by a tendency to fail beginning about seven to ten years following implantation. Valve degeneration is particularly rapid in young patients and during pregnancy. Calcification, i.e., the deposition of calcium salts, especially calcium phosphate (hydroxyapatite), appears to be a major cause of degeneration. Flexible polymer heart valves also tend to fail due to calcification and subsequent degeneration.
Native heart valve tissue with viable cells has natural protection against calcification. Endothelial cells that coat the blood contacting surfaces of a native valve provide a barrier against calcification. These cells also protect against infection and provide active thromboresistance.
In a first aspect, the invention pertains to a medical article suitable for contacting a patient""s bodily fluids. The medical article includes a biocompatible material and at least one cell adhesion stimulating protein associated with the biocompatible material. The biocompatible material includes a ceramic material over at least part of its surface.
In another aspect, the invention pertains to a method for producing a medical article suitable for contact with a patient""s bodily fluids. The method includes the adhering of a cell adhesion stimulating protein to a ceramic material.
In a further aspect, the invention pertains to a method for producing a prosthesis. The method includes the harvesting of viable cells from a patient and the adhering of a cell adhesion stimulating protein to a ceramic material. The method further includes the associating of the viable cells with the ceramic material by contacting the ceramic material having adhered protein with a cell culture comprising the viable cells.